Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells

Dustin J Flanagan; Toby J Phesse; Nick Barker; Renate H M Schwab; Nancy Amin; Jordane Malaterre; Daniel E Stange; Cameron J Nowell; Scott A Currie; Jarel T S Saw; Eva Beuchert; Robert G Ramsay; Owen J Sansom; Matthias Ernst; Hans Clevers; Elizabeth Vincan

doi:10.1016/j.stemcr.2015.03.003

Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells

Dustin J Flanagan, Toby J Phesse, Nick Barker, Renate H M Schwab, Nancy Amin, Jordane Malaterre, Daniel E Stange, Cameron J Nowell, Scott A Currie, Jarel T S Saw, Eva Beuchert, Robert G Ramsay, Owen J Sansom, Matthias Ernst, Hans Clevers, Elizabeth Vincan

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cells intermingled with Paneth cells at the base of crypts. These crypt base stem cells exclusively express Lgr5 and require Wnt3 or, in its absence, Wnt2b. However, the Frizzled (Fzd) receptor that transmits these Wnt signals is unknown. We determined the expression profile of Fzd receptors in Lgr5(+) stem cells, their immediate daughter cells, and Paneth cells. Here we show Fzd7 is enriched in Lgr5(+) stem cells and binds Wnt3 and Wnt2b. Conditional deletion of the Fzd7 gene in adult intestinal epithelium leads to stem cell loss in vivo and organoid death in vitro. Crypts of conventional Fzd7 knockout mice show decreased basal Wnt signaling and impaired capacity to regenerate the epithelium following deleterious insult. These observations indicate that Fzd7 is required for robust Wnt-dependent processes in Lgr5(+) intestinal stem cells.

Original language	English
Pages (from-to)	759-67
Number of pages	9
Journal	Stem Cell Reports [E]
Volume	4
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2015.03.003
Publication status	Published - 2015

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Flanagan, D. J., Phesse, T. J., Barker, N., Schwab, R. H. M., Amin, N., Malaterre, J., Stange, D. E., Nowell, C. J., Currie, S. A., Saw, J. T. S., Beuchert, E., Ramsay, R. G., Sansom, O. J., Ernst, M., Clevers, H., & Vincan, E. (2015). Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells. Stem Cell Reports [E], 4(5), 759-67. https://doi.org/10.1016/j.stemcr.2015.03.003

@article{359b515e2f8746d8a2627979931d29f0,

title = "Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells",

abstract = "The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cells intermingled with Paneth cells at the base of crypts. These crypt base stem cells exclusively express Lgr5 and require Wnt3 or, in its absence, Wnt2b. However, the Frizzled (Fzd) receptor that transmits these Wnt signals is unknown. We determined the expression profile of Fzd receptors in Lgr5(+) stem cells, their immediate daughter cells, and Paneth cells. Here we show Fzd7 is enriched in Lgr5(+) stem cells and binds Wnt3 and Wnt2b. Conditional deletion of the Fzd7 gene in adult intestinal epithelium leads to stem cell loss in vivo and organoid death in vitro. Crypts of conventional Fzd7 knockout mice show decreased basal Wnt signaling and impaired capacity to regenerate the epithelium following deleterious insult. These observations indicate that Fzd7 is required for robust Wnt-dependent processes in Lgr5(+) intestinal stem cells.",

author = "Flanagan, {Dustin J} and Phesse, {Toby J} and Nick Barker and Schwab, {Renate H M} and Nancy Amin and Jordane Malaterre and Stange, {Daniel E} and Nowell, {Cameron J} and Currie, {Scott A} and Saw, {Jarel T S} and Eva Beuchert and Ramsay, {Robert G} and Sansom, {Owen J} and Matthias Ernst and Hans Clevers and Elizabeth Vincan",

year = "2015",

doi = "10.1016/j.stemcr.2015.03.003",

language = "English",

volume = "4",

pages = "759--67",

journal = "Stem Cell Reports [E]",

issn = "2213-6711",

publisher = "Cell Press",

number = "5",

}

Flanagan, DJ, Phesse, TJ, Barker, N, Schwab, RHM, Amin, N, Malaterre, J, Stange, DE, Nowell, CJ, Currie, SA, Saw, JTS, Beuchert, E, Ramsay, RG, Sansom, OJ, Ernst, M, Clevers, H & Vincan, E 2015, 'Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells', Stem Cell Reports [E], vol. 4, no. 5, pp. 759-67. https://doi.org/10.1016/j.stemcr.2015.03.003

TY - JOUR

T1 - Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells

AU - Flanagan, Dustin J

AU - Phesse, Toby J

AU - Barker, Nick

AU - Schwab, Renate H M

AU - Amin, Nancy

AU - Malaterre, Jordane

AU - Stange, Daniel E

AU - Nowell, Cameron J

AU - Currie, Scott A

AU - Saw, Jarel T S

AU - Beuchert, Eva

AU - Ramsay, Robert G

AU - Sansom, Owen J

AU - Ernst, Matthias

AU - Clevers, Hans

AU - Vincan, Elizabeth

PY - 2015

Y1 - 2015

N2 - The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cells intermingled with Paneth cells at the base of crypts. These crypt base stem cells exclusively express Lgr5 and require Wnt3 or, in its absence, Wnt2b. However, the Frizzled (Fzd) receptor that transmits these Wnt signals is unknown. We determined the expression profile of Fzd receptors in Lgr5(+) stem cells, their immediate daughter cells, and Paneth cells. Here we show Fzd7 is enriched in Lgr5(+) stem cells and binds Wnt3 and Wnt2b. Conditional deletion of the Fzd7 gene in adult intestinal epithelium leads to stem cell loss in vivo and organoid death in vitro. Crypts of conventional Fzd7 knockout mice show decreased basal Wnt signaling and impaired capacity to regenerate the epithelium following deleterious insult. These observations indicate that Fzd7 is required for robust Wnt-dependent processes in Lgr5(+) intestinal stem cells.

AB - The mammalian adult small intestinal epithelium is a rapidly self-renewing tissue that is maintained by a pool of cycling stem cells intermingled with Paneth cells at the base of crypts. These crypt base stem cells exclusively express Lgr5 and require Wnt3 or, in its absence, Wnt2b. However, the Frizzled (Fzd) receptor that transmits these Wnt signals is unknown. We determined the expression profile of Fzd receptors in Lgr5(+) stem cells, their immediate daughter cells, and Paneth cells. Here we show Fzd7 is enriched in Lgr5(+) stem cells and binds Wnt3 and Wnt2b. Conditional deletion of the Fzd7 gene in adult intestinal epithelium leads to stem cell loss in vivo and organoid death in vitro. Crypts of conventional Fzd7 knockout mice show decreased basal Wnt signaling and impaired capacity to regenerate the epithelium following deleterious insult. These observations indicate that Fzd7 is required for robust Wnt-dependent processes in Lgr5(+) intestinal stem cells.

U2 - 10.1016/j.stemcr.2015.03.003

DO - 10.1016/j.stemcr.2015.03.003

M3 - Article

C2 - 25892522

SN - 2213-6711

VL - 4

SP - 759

EP - 767

JO - Stem Cell Reports [E]

JF - Stem Cell Reports [E]

IS - 5

ER -

Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5(+) stem cells

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